Sterculic acid, 8-(2-octacyclopropen-1-yl)octanoic acid:
is a naturally occurring cyclopropene acid present in kapok seed oil, cottonseed oil, and in the seeds of the Sterculia foetida tree. Sterculic acid has been reported to be a non-specific inhibitor of stearoyl-Co desaturase (SCD), which has been implicated in several disease states, including cardiovascular disease, obesity, non-insulin-dependent diabetes mellitus, skin disease, hypertension, neurological diseases, immune disorders and cancer. Ntambi, J. Lipid Res., 1990, 40, 1549-1558. Sterculic acid, however, has not been found to be useful in vivo because at physiological doses, it is not selective for SCD and inhibits other desaturases. See U.S. Published Application 2007/0219211 at [0006].
Sterculic acid's ability to increase the stearic:oleic acid ratio has led to suggestions that sterculic acid might inhibit tumor growth. But while some researchers have reported that sterculic acid can inhibit malignant cell growth in vitro, others have reported that sterculic acid is actually a promoter of 2′ acetoaminofluorene-induced liver carcinogenesis and that when applied to hepatoma cells, inhibition of doubling time was observed. Khoo, et al. Manipulation of body fat composition with sterculic acid can inhibit mammary carcinomas in vivo, Br. J. Cancer (1991), 63, 97-101.
7-Ketocholesterol (7KCh) is a major oxidation product of cholesterol and is found in atherosclerotic plaques. Accumulation of 7-ketocholesterol in lipoprotein deposits is suspected of causing macrophage foam cell formation resulting in atheromatous plaques. In addition to a role in atherosclerosis, 7-ketocholesterol cytotoxicity has been implicated in the pathogenesis of Alzheimer's disease, age-related macular degeneration, and some forms of cancer. To date, no compounds have been demonstrated to inhibit 7-ketocholesterol-mediated inflammation and cytotoxicity. As a result, treatments for diseases associated with 7-ketocholesterol accumulation are needed.
Angiogenesis is the development of new blood vessels from preexisting ones and is an important natural process that occurs in the body, both in health and in disease. In physiological conditions such as pregnancy and wound healing, angiogenesis is tightly regulated. In pathological conditions, however, such as inflammatory diseases, tumor growth, and tumor metastasis, a chronic “unregulated” angiogenic state often exacerbates the disease. Excessive growth of blood vessels or neovascularization has been shown to be a causative factor in many diseases such as cancer and diabetic retinopathy. Anti-angiogenic therapies aimed at halting new blood vessel growth is an active field of research.
Wet age-related macular degeneration (wet AMD) is an example of a disease state characterized by abnormal blood vessel formation (angiogenesis) under the retina and macula. These new blood vessels may bleed and leak fluid, causing the macula to bulge, distorting or destroying vision in the affected eye. To date, very few treatments exist for the management of wet macular degeneration. Presently, patients receive repeated intravitreal injections of anti-VEGF antibodies directly into the eye. Such treatments are expensive and are stressful to the patient. Thus, new, less invasive treatments are needed to treat wet AMD.